Cyclic nucleotides and protein phosphorylation play a special role in photoreceptor control mechanisms. 1. A calcium phospholipid-dependent protein kinase (C-kinase) phosphorylates specific proteins of the rod outer segment organelle. 2. A specific extracellular cyclic GMP phosphodiesterase was identified in the retinal extracellular matrix. 3. Cyclic AMP-dependent protein kinases were found to be abnormal in human retinoblastoma cells in culture. 4. Cyclic GMP was found to be abnormally high in photoreceptor cell synapses of an animal model of inherited retinal degeneration.